NCT01712490 · CITED IN SOURCE DOCUMENTS

A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-02-27

This open-label, randomized, 2-arm, multicenter, phase 3 study has the primary objective of comparing the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin \[Adriamycin\], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin \[Adriamycin\],bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma(HL)

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF

→

outcome · POSTED

Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)

→

outcome · POSTED

Number of Participants With Abnormal Clinical Laboratory Values

→

outcome · POSTED

Event-free Survival (EFS) Per IRF

→

outcome · POSTED

Disease-free Survival (DFS) Per IRF

→

outcome · POSTED

Overall Response Rate (ORR) Per IRF

→

outcome · POSTED

Duration of Response (DOR) Per IRF

→

outcome · POSTED

Duration of Complete Remission (DOCR) Per IRF

→

outcome · POSTED

Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy

→

outcome · POSTED

Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy

→

outcome · POSTED

Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2

→

outcome · POSTED

A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb)

→

outcome · POSTED

A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE)

→

outcome · POSTED

A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb

→

outcome · POSTED

A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE

→

outcome · POSTED

A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin

→

outcome · POSTED

Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: 1. Treatment-naïve participants with Ann Arbor Stage III or IV HL. 2. Histologically confirmed classical Hodgkin Lymphoma (HL) according to the current World Health Organization (WHO) classification. 3. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 2. 4. Bidimensional measurable disease as documented by radiographic technique per the International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma. Exclusion Criteria: 1. Nodular lymphocyte predominant Hodgkin lymphoma. 2. Cerebral/meningeal disease, including signs and symptoms of progressive multifocalleukoencephalopathy (PML). 3. Sensory or motor peripheral neuropathy. 4. Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 12 weeks of first study drug dose. 5. Known human immunodeficiency virus (HIV) positive. 6. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection. Please note that there are additional exclusion criteria. The study center will determine if you meet all of the criteria.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 milligram per kilogram (mg/kg) plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine (DTIC) 375 mg/m\^2.
intervention Names
Drug: brentuximab vedotin
Drug: doxorubicin
Drug: vinblastine
Drug: dacarbazine
label
A + AVD
type
EXPERIMENTAL
description
ABVD consists of doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine (DTIC) 375 mg/m\^2.
intervention Names
Drug: doxorubicin
Drug: bleomycin
Drug: vinblastine
Drug: dacarbazine
label
ABVD
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
A + AVD
description
Brentuximab vedotin (ADCETRIS®)1.2 mg/kg by IV infusion on Days 1 and 15 of each 28-day cycle.
name
brentuximab vedotin
other Names
ADCETRIS®
SGN-35
type
DRUG
arm Group Labels
A + AVD
ABVD
description
Doxorubicin: 25 mg/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
name
doxorubicin
other Names
Adriamycin
type
DRUG
arm Group Labels
ABVD
description
Bleomycin: 10 units/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
name
bleomycin
type
DRUG
arm Group Labels
A + AVD
ABVD
description
Vinblastine: 6 mg/m2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle
name
vinblastine
type
DRUG
arm Group Labels
A + AVD
ABVD
description
Dacarbazine (DTIC): 375 mg/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
name
dacarbazine
other Names
DTIC
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1334
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
mPFS was defined as the time from the date of randomization to the date of the first of documentation of progressive disease (PD), death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for Hodgkin lymphoma (HL) after completion of frontline therapy. PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Frontline therapy is the part of standard set of treatments.
measure
Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
time Frame
Baseline until PD or death or receipt of any subsequent anticancer therapy for HL after completion of frontline therapy (approximately up to 4 years)

secondary Outcomes

description
OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis were censored at the date last known to be alive.
measure
Overall Survival (OS)
time Frame
Baseline until death (approximately up to 4 years)
description
CR rate at the end of randomized regimen per investigator was defined as the percentage of participants who achieved CR at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by IRF. CR was defined as disappearance of all evidence of disease.
measure
Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF
time Frame
Baseline up to end of randomized regimen (approximately 1 year)
measure
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
time Frame
Baseline up to 30 days after last dose of study drug (approximately 1 year)
measure
Number of Participants With Abnormal Clinical Laboratory Values
time Frame
Baseline up to 30 days after last dose of study drug (approximately 1 year)
description
EFS was defined as the time from randomization until any cause of treatment failure: PD, premature discontinuation of randomized treatment for any reason, or death due to any cause, whichever occurs first. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir per IRF.
measure
Event-free Survival (EFS) Per IRF
time Frame
Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years)
description
DFS per IRF was defined as the time from CR to disease progression as determined by an IRF or to death from lymphoma or acute toxicity from treatment. CR was defined as disappearance of all evidence of disease.
measure
Disease-free Survival (DFS) Per IRF
time Frame
From CR until PD or death (approximately up to 4 years)
description
ORR per IRF was defined as the percentage of participants who achieved CR or partial remission (PR) at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by an IRF. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
measure
Overall Response Rate (ORR) Per IRF
time Frame
Baseline up to end of randomized regimen (approximately 1 year)
description
DOR per IRF in participants with response was the time between first documentation of response (PR or CR) and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
measure
Duration of Response (DOR) Per IRF
time Frame
From first documented response until PD (approximately 4 years)
description
DOCR per IRF in participants with CR was the time between first documentation of CR and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease.
measure
Duration of Complete Remission (DOCR) Per IRF
time Frame
From first documentation of CR until PD (approximately 4 years)
description
CR was defined as disappearance of all evidence of disease as determined by an IRF.
measure
Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy
time Frame
Baseline up to end of frontline therapy (approximately 4 years)
description
CR rate at the end of frontline therapy per IRF was defined as the percentage of participants who achieved CR at the end of frontline therapy that is after completion of either randomized regimen or alternate frontline therapy as determined by an IRF. CR was defined as disappearance of all evidence of disease.
measure
Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy
time Frame
Baseline up to end of frontline therapy (approximately 4 years)
description
PET negativity rate at Cycle 2 was defined as the percentage of participants with negative Cycle 2 PET results defined as Deauville score less than or equal to (\<=) 3 at Cycle 2. The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans.
measure
Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2
time Frame
Cycle 2 Day 25

Full study description

brief Summary: This open-label, randomized, 2-arm, multicenter, phase 3 study has the primary objective of comparing the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin \[Adriamycin\], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin \[Adriamycin\],bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma(HL)

Source references

references

citation
Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.
pmid
40135712
type
DERIVED
citation
Crosswell HE, LaCasce AS, Bartlett NL, Straus DJ, Savage KJ, Zinzani PL, Collins GP, Fanale M, Fenton K, Dong C, Miao H, Grigg AP. Brentuximab vedotin with chemotherapy in adolescents and young adults with stage III or IV classical Hodgkin lymphoma in ECHELON-1. Haematologica. 2024 Mar 1;109(3):982-987. doi: 10.3324/haematol.2023.283303. No abstract available.
pmid
37794803
type
DERIVED
citation
Ansell SM, Radford J, Connors JM, Dlugosz-Danecka M, Kim WS, Gallamini A, Ramchandren R, Friedberg JW, Advani R, Hutchings M, Evens AM, Smolewski P, Savage KJ, Bartlett NL, Eom HS, Abramson JS, Dong C, Campana F, Fenton K, Puhlmann M, Straus DJ; ECHELON-1 Study Group. Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2022 Jul 28;387(4):310-320. doi: 10.1056/NEJMoa2206125. Epub 2022 Jul 13.
pmid
35830649
type
DERIVED
citation
Evens AM, Connors JM, Younes A, Ansell SM, Kim WS, Radford J, Feldman T, Tuscano J, Savage KJ, Oki Y, Grigg A, Pocock C, Dlugosz-Danecka M, Fenton K, Forero-Torres A, Liu R, Jolin H, Gautam A, Gallamini A. Older patients (aged >/=60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study. Haematologica. 2022 May 1;107(5):1086-1094. doi: 10.3324/haematol.2021.278438.
pmid
34162178
type
DERIVED
citation
Straus DJ, Dlugosz-Danecka M, Connors JM, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Ramchandren R, Zinzani PL, Hutchings M, Munoz J, Lee HJ, Kim WS, Advani R, Ansell SM, Younes A, Gallamini A, Liu R, Little M, Fenton K, Fanale M, Radford J. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021 Jun;8(6):e410-e421. doi: 10.1016/S2352-3026(21)00102-2.
pmid
34048680
type
DERIVED
citation
Straus DJ, Dlugosz-Danecka M, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Ramchandren R, Zinzani PL, Hutchings M, Connors JM, Radford J, Munoz J, Kim WS, Advani R, Ansell SM, Younes A, Miao H, Liu R, Fenton K, Forero-Torres A, Gallamini A. Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study. Blood. 2020 Mar 5;135(10):735-742. doi: 10.1182/blood.2019003127.
pmid
31945149
type
DERIVED
citation
Ramchandren R, Advani RH, Ansell SM, Bartlett NL, Chen R, Connors JM, Feldman T, Forero-Torres A, Friedberg JW, Gopal AK, Gordon LI, Kuruvilla J, Savage KJ, Younes A, Engley G, Manley TJ, Fenton K, Straus DJ. Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma. Clin Cancer Res. 2019 Mar 15;25(6):1718-1726. doi: 10.1158/1078-0432.CCR-18-2435. Epub 2019 Jan 7.
pmid
30617130
type
DERIVED
citation
Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J; ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018 Jan 25;378(4):331-344. doi: 10.1056/NEJMoa1708984. Epub 2017 Dec 10.
pmid
29224502
type
DERIVED
citation
Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. doi: 10.1016/S1470-2045(13)70501-1. Epub 2013 Nov 15.
pmid
24239220
type
DERIVED